DE102004004965B4 - Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates - Google Patents
Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates Download PDFInfo
- Publication number
- DE102004004965B4 DE102004004965B4 DE102004004965A DE102004004965A DE102004004965B4 DE 102004004965 B4 DE102004004965 B4 DE 102004004965B4 DE 102004004965 A DE102004004965 A DE 102004004965A DE 102004004965 A DE102004004965 A DE 102004004965A DE 102004004965 B4 DE102004004965 B4 DE 102004004965B4
- Authority
- DE
- Germany
- Prior art keywords
- formula
- transfer catalyst
- ethoxymethyl
- ethyl bromide
- phase transfer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims description 6
- 150000003813 tropane derivatives Chemical class 0.000 title claims description 6
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000003085 diluting agent Substances 0.000 claims abstract description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 26
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 18
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 239000012074 organic phase Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- YTEQCFHEANIYBU-FHZGLPGMSA-N (1r,5r)-4-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane Chemical class C1CC(COCC)[C@@]2([H])CC[C@]1([H])N2C YTEQCFHEANIYBU-FHZGLPGMSA-N 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- -1 cyano-substituted phenyl Chemical group 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 235000011118 potassium hydroxide Nutrition 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- ZIVJUFNVDKADJT-BEDQTAKTSA-N (1s,3s,4r,5r)-3-(3,4-dichlorophenyl)-4-(ethoxymethyl)-8-methyl-8-azabicyclo[3.2.1]octane;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1([C@@H]2[C@@H](COCC)[C@]3(CC[C@@](C2)(N3C)[H])[H])=CC=C(Cl)C(Cl)=C1 ZIVJUFNVDKADJT-BEDQTAKTSA-N 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YZOJGDVBJLRATM-FUTJPDQTSA-N [(1s,3s,4r,5r)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-4-yl]methanol Chemical compound C1([C@@H]2[C@@H](CO)[C@]3(CC[C@@](C2)(N3C)[H])[H])=CC=C(Cl)C(Cl)=C1 YZOJGDVBJLRATM-FUTJPDQTSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 150000001860 citric acid derivatives Chemical class 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- ZUZLIXGTXQBUDC-UHFFFAOYSA-N methyltrioctylammonium Chemical class CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC ZUZLIXGTXQBUDC-UHFFFAOYSA-N 0.000 description 2
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 2
- DTIFFPXSSXFQCJ-UHFFFAOYSA-N tetrahexylazanium Chemical compound CCCCCC[N+](CCCCCC)(CCCCCC)CCCCCC DTIFFPXSSXFQCJ-UHFFFAOYSA-N 0.000 description 2
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- HJHUXWBTVVFLQI-UHFFFAOYSA-N tributyl(methyl)azanium Chemical compound CCCC[N+](C)(CCCC)CCCC HJHUXWBTVVFLQI-UHFFFAOYSA-N 0.000 description 2
- 0 *C(CC1CC2)C(CO)C2N1I Chemical compound *C(CC1CC2)C(CO)C2N1I 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- RZXLPPRPEOUENN-UHFFFAOYSA-N Chlorfenson Chemical compound C1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=C(Cl)C=C1 RZXLPPRPEOUENN-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid Chemical class OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 230000006203 ethylation Effects 0.000 description 1
- 238000006200 ethylation reaction Methods 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002023 somite Anatomy 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VCVWXKKWDOJNIT-ZOMKSWQUSA-N tesofensine Chemical compound C1([C@H]2C[C@@H]3CC[C@@H](N3C)[C@@H]2COCC)=CC=C(Cl)C(Cl)=C1 VCVWXKKWDOJNIT-ZOMKSWQUSA-N 0.000 description 1
- 125000005497 tetraalkylphosphonium group Chemical group 0.000 description 1
- CHYBTAZWINMGHA-UHFFFAOYSA-N tetraoctylazanium Chemical class CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)CCCCCCCC CHYBTAZWINMGHA-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- IPILPUZVTYHGIL-UHFFFAOYSA-M tributyl(methyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](C)(CCCC)CCCC IPILPUZVTYHGIL-UHFFFAOYSA-M 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (18)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004004965A DE102004004965B4 (de) | 2004-01-31 | 2004-01-31 | Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates |
| DE502005008535T DE502005008535D1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2- (ethoxymethyl)-tropanderivates |
| AU2005209382A AU2005209382B2 (en) | 2004-01-31 | 2005-01-20 | Method for producing a 2-(ethoxymethyl)tropane derivative |
| EP05701061A EP1713800B1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2- (ethoxymethyl)-tropanderivates |
| NZ548092A NZ548092A (en) | 2004-01-31 | 2005-01-20 | Method for producing a 2-(ethoxymethyl)tropane derivative |
| PCT/EP2005/000512 WO2005073228A1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2-(ethoxymethyl)-tropanderivates |
| HK07104270.6A HK1097845B (zh) | 2004-01-31 | 2005-01-20 | 制备2-(乙氧基甲基)-托烷衍生物的方法 |
| CA002554125A CA2554125A1 (en) | 2004-01-31 | 2005-01-20 | Method for producing a 2-(ethoxymethyl)tropane derivative |
| AT05701061T ATE449095T1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2- (ethoxymethyl)-tropanderivates |
| JP2006550028A JP2007519660A (ja) | 2004-01-31 | 2005-01-20 | ２−（エトキシメチル）トロパン誘導体の製造方法 |
| CN2005800027516A CN1910180B (zh) | 2004-01-31 | 2005-01-20 | 制备2-(乙氧基甲基)-托烷衍生物的方法 |
| DK05701061.3T DK1713800T3 (da) | 2004-01-31 | 2005-01-20 | Fremgangsmåde til fremstilling af et 2(ethoxymethyl)tropanderivat |
| TW094102759A TWI338690B (en) | 2004-01-31 | 2005-01-28 | Improved process for the preparation of (ethoxymethyl)-tropane derivatives |
| ARP050100301A AR047515A1 (es) | 2004-01-31 | 2005-01-28 | PROCEDIMIENTO PARA LA PREPARACIoN DE UN DERIVADO DE 2-(ETOXIMETIL)-TROPANO |
| UY28730A UY28730A1 (es) | 2004-01-31 | 2005-01-28 | Procedimiento mejorado para la preparacion de un derivado de 2-(etoximetil)-tropano |
| PE2005000107A PE20050770A1 (es) | 2004-01-31 | 2005-01-28 | Procedimiento mejorado para la preparacion de un derivado de 2-(etoximetil)-tropano |
| MYPI20050353A MY141935A (en) | 2004-01-31 | 2005-01-28 | Improved process for the preparation of (ethoxymethyl)-tropan derivatives |
| US11/047,260 US7544802B2 (en) | 2004-01-31 | 2005-01-31 | Process for the preparation of 2-(ethoxymethyl)-tropane derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004004965A DE102004004965B4 (de) | 2004-01-31 | 2004-01-31 | Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE102004004965A1 DE102004004965A1 (de) | 2005-09-01 |
| DE102004004965B4 true DE102004004965B4 (de) | 2006-01-05 |
Family
ID=34801391
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102004004965A Expired - Fee Related DE102004004965B4 (de) | 2004-01-31 | 2004-01-31 | Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates |
| DE502005008535T Expired - Lifetime DE502005008535D1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2- (ethoxymethyl)-tropanderivates |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE502005008535T Expired - Lifetime DE502005008535D1 (de) | 2004-01-31 | 2005-01-20 | Verfahren zur herstellung eines 2- (ethoxymethyl)-tropanderivates |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7544802B2 (https=) |
| EP (1) | EP1713800B1 (https=) |
| JP (1) | JP2007519660A (https=) |
| CN (1) | CN1910180B (https=) |
| AR (1) | AR047515A1 (https=) |
| AT (1) | ATE449095T1 (https=) |
| AU (1) | AU2005209382B2 (https=) |
| CA (1) | CA2554125A1 (https=) |
| DE (2) | DE102004004965B4 (https=) |
| DK (1) | DK1713800T3 (https=) |
| MY (1) | MY141935A (https=) |
| NZ (1) | NZ548092A (https=) |
| PE (1) | PE20050770A1 (https=) |
| TW (1) | TWI338690B (https=) |
| UY (1) | UY28730A1 (https=) |
| WO (1) | WO2005073228A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2017324406A1 (en) | 2016-09-07 | 2019-05-02 | Saniona A/S | Tesofensine compositions |
| CN115572289A (zh) * | 2022-10-24 | 2023-01-06 | 龙曦宁（上海）医药科技有限公司 | 一种特索芬辛的合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997030997A1 (en) * | 1996-02-22 | 1997-08-28 | Neurosearch A/S | Tropane-derivatives, their preparation and use |
| WO2002102801A1 (en) * | 2001-05-23 | 2002-12-27 | Neurosearch A/S | Tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003045388A1 (en) * | 2001-11-30 | 2003-06-05 | Neurosearch A/S | Tropane derivatives having dopamine reuptake inhibitor activity for the treatment of ischemic diseases |
| WO2021028011A1 (en) | 2019-08-09 | 2021-02-18 | Quintus Technologies Ab | System and method for handling and isostatic pressure treatment of a load |
-
2004
- 2004-01-31 DE DE102004004965A patent/DE102004004965B4/de not_active Expired - Fee Related
-
2005
- 2005-01-20 DE DE502005008535T patent/DE502005008535D1/de not_active Expired - Lifetime
- 2005-01-20 JP JP2006550028A patent/JP2007519660A/ja active Pending
- 2005-01-20 EP EP05701061A patent/EP1713800B1/de not_active Expired - Lifetime
- 2005-01-20 CN CN2005800027516A patent/CN1910180B/zh not_active Expired - Fee Related
- 2005-01-20 NZ NZ548092A patent/NZ548092A/xx unknown
- 2005-01-20 AT AT05701061T patent/ATE449095T1/de active
- 2005-01-20 WO PCT/EP2005/000512 patent/WO2005073228A1/de not_active Ceased
- 2005-01-20 CA CA002554125A patent/CA2554125A1/en not_active Abandoned
- 2005-01-20 AU AU2005209382A patent/AU2005209382B2/en not_active Expired - Fee Related
- 2005-01-20 DK DK05701061.3T patent/DK1713800T3/da active
- 2005-01-28 TW TW094102759A patent/TWI338690B/zh active
- 2005-01-28 PE PE2005000107A patent/PE20050770A1/es not_active Application Discontinuation
- 2005-01-28 AR ARP050100301A patent/AR047515A1/es unknown
- 2005-01-28 MY MYPI20050353A patent/MY141935A/en unknown
- 2005-01-28 UY UY28730A patent/UY28730A1/es not_active Application Discontinuation
- 2005-01-31 US US11/047,260 patent/US7544802B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997030997A1 (en) * | 1996-02-22 | 1997-08-28 | Neurosearch A/S | Tropane-derivatives, their preparation and use |
| WO2002102801A1 (en) * | 2001-05-23 | 2002-12-27 | Neurosearch A/S | Tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1910180B (zh) | 2010-05-12 |
| DE102004004965A1 (de) | 2005-09-01 |
| NZ548092A (en) | 2009-07-31 |
| EP1713800B1 (de) | 2009-11-18 |
| CA2554125A1 (en) | 2005-08-11 |
| AU2005209382A1 (en) | 2005-08-11 |
| HK1097845A1 (zh) | 2007-07-06 |
| US20050171145A1 (en) | 2005-08-04 |
| CN1910180A (zh) | 2007-02-07 |
| WO2005073228A1 (de) | 2005-08-11 |
| AR047515A1 (es) | 2006-01-25 |
| PE20050770A1 (es) | 2005-11-10 |
| UY28730A1 (es) | 2005-09-30 |
| US7544802B2 (en) | 2009-06-09 |
| TW200538455A (en) | 2005-12-01 |
| EP1713800A2 (de) | 2006-10-25 |
| AU2005209382B2 (en) | 2011-02-17 |
| WO2005073228A8 (de) | 2005-10-27 |
| DE502005008535D1 (de) | 2009-12-31 |
| ATE449095T1 (de) | 2009-12-15 |
| TWI338690B (en) | 2011-03-11 |
| JP2007519660A (ja) | 2007-07-19 |
| DK1713800T3 (da) | 2010-03-29 |
| MY141935A (en) | 2010-07-30 |
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Owner name: NEUROSEARCH A/S, BALLERUP, DK |
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Representative=s name: GRUENECKER, KINKELDEY, STOCKMAIR & SCHWANHAEUSSER |
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| R119 | Application deemed withdrawn, or ip right lapsed, due to non-payment of renewal fee |
Effective date: 20120801 |